Normal cell progression to their malignant derivatives is associated with remodeling of the proteins controlling such major cellular functions as apoptosis and proliferation. Here, we show that prostate cancer cells use ORAI and TRP protein redistribution as an oncogenic switch mechanism. In particular, ORAI3 and TRPV6 remodeling results from genomic and microenvironment perturbations that disrupt the equilibrium of channels and favors the formation of novel Ca2+ channels activated in a store-independent manner. This remodeling of Ca2+ signaling in turn induces cell progression to a more aggressive pro-proliferative phenotype. Our study specifically positions these channels at the center of molecular machinery linking dysregulated arachidonic acid metabolism, calcium homeostasis, and oncogenesis.
Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, SA093
Research Symposium: Remodeling of channel-forming TRP and ORAI proteins determines an oncogenic switch in prostate cancer
N. Prevarskaya1, C. Dubois1, V. Fabien1, L. V'yacheslav1, R. Maylis1
1. Laboratoire de physiologie cellulaire inserm u1003, Villeneuve d'Ascq, France.
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.